We are able to reproducibly elicit lethal pulmonary lesions with nitrofurantoin (NF) in rats, in a dose-dependent fashion. This indicates that NF-induced lung disease in man may be the result of a direct pulmonary toxicity, and not an immune response as is widely believed. Other studies indicate that NF can be metabolized to highly reactive chemical species; we are, therefore, investigating the possibility that metabolic activation is involved in the production of lung lesions by NF.